Understanding the effect of nitrosylation on dynamics of human epidermal growth factor: a µs simulation study

Abstract

Abstract Advancements in plasma science, such as the development cold atmospheric plasmas made it possible to easily generate reactive oxygen and nitrogen species (RONS) and apply them onto biological media at ambient conditions. Studying the interactions of RONS with biomolecules is a central topic of plasma medicine. One of the main targets of plasma medicine is to take control over signaling proteins such as human epidermal growth factor (hEGF) which is important protein in cancer treatment and wound healing. The oxidative damage of RONS on various proteins, including hEGF, was investigated using molecular dynamics (MD) simulations. However, another effect of RONS—nitrosative damage—is left unexplored. Plasma treatment can induce substantial damage via nitrosylation by reactive nitrogen species. Thus, elucidating effects of nitrosylation on protein structures is crucial, especially in plasma medicine. Here, we perform MD simulations to explore the effect of nitrosylation on the conformation of hEGF. We carried out MD simulations with different degrees of modifications of hEGF structures to mimic short and long plasma exposure times. Our results show that the nitrosylation induces conformational changes in hEGF and the breakage of disulfide bonds which might modulate binding of hEGF with its receptor. But the structural stability of hEGF remains almost unchallenged to the nitrosative damage, even to the disruption of disulfide bonds. The results assist plasma medicine applications in cancer treatment and wound healing by modulating plasma treatment time and chemical compositions of plasma-generated RONS to mediate effective oxidation of biological environment and develop optimal treatment protocols.